1-pyrrolidyl esters



Patented Oct. 13, 1953 2,655,511 l-PYRROLIDYL ESTERS Eugene H. Woodrufl, Kalamazoo, Mich., assignor to The Upjohn Company,

Kalamazoo, Mich.,

a corporation of Michigan N 0 Drawing. Application November 18, 1950, Serial No. 196,525

6 Claims. (01. 260-3263) This invention relates to l-pyrrolidyl esters having the formula:

in which X is hydrogen or an alkyl radical, Y is a monocyclic hydrocarbon radical, e. g., an aryl, aralkyl, cycloalkyl, or cycloalkenyl radical, Z is an alkyl or a m'onocyclic hydrocarbon radical,

tion the pyrrolidyl radical is joined to the adjacent CnHzn group through the nitrogen atom of the pyrrolidyl nucleus, and for simplicity in namdrochlorides, hydrobromides, sulfates, benzoates, nitrobenzoates, acetates, succinates, citrates, nitrates, p-toluenesulfonates and other acid addition salts acetate and lower temperatures.

Members of this new group of compounds have been prepared and found to have value as antispasmodics and as intermediates for the preparation of more complex organic compounds. These compounds have exhibited most desirable antispasmodic properties, having effects similar to nervous system. Papaverine, an opium alkaloid,

is considered to be a musculotropic agent capable of acting on smooth muscle tissues directly to relieve spasm intrinsic in the muscle tissues.

In clinical practice it is not always possible to determine which type of spasm is present. Furthermore, both types may be present, simultaneously presenting a situation in which an antispasdomic agent effective against only a single type is of limited utility. The compounds with which the present invention is concerned possess both musculotropic and neurotropic activity, and, upon administration, exhibit a dual antispasmod-ic effectiveness of suilicient degree to render them useful in treating either of the previously mentioned types of spasm, or both simultaneously, if they should be present.

The free basic esters of the invention can be prepared readily by reacting an acid chloride having the formula:

t with a (l-pyrrolidyDalkanol (which is also designated a l-(hydroxyalkyl)tetrahydropyrrole) having the formula:

(lower alkyl). ,1 O Ho c,.H2.N +HB-m in which X, Y, Z, m and n have the significance specified hereinbefore. The corresponding acid bromides can also be used, if desired, although the preparation of compounds of this invention will be described with particular reference to the acid chlorides. The specified acid chlorides can be prepared readily and in excellent yields by heating the corresponding acid with thionyl chloride for a period of from one to several hours at the reflux temperature of the mixture. An excess of thionyl chloride is usually employed and the excess can subsequently be removed by distillation in vacuo leaving the acid chloride as a residue, generally sufficiently pure for use without further purification, but it can be fractionally distilled, if greater purity is desired. Acid bromides can be prepared in similar fashion using th ionyl bromide.

(l-pyrrolidyl) alkanols used for the production of the esters of the invention can be prepared in several ways. Thus, a suitable haloalkanol can be reacted with pyrrolidine or with a C-alkylsubstituted pyrrolidine and the desired (l-pyrrolidyl) alkanol obtained. In certain instances, it is advantageous first to condense pyrrolidine or a C-alkyl-pyrrolidine with a suitable haloketone, halo-aldehyde, an ester of a suitable saturated halo-aliphatic acid, or an ester of a suitable alpha, beta-unsaturated aliphatic acid to form the corresponding l-pyrrolidyl compound. In some instances, it may be of advantage to condense a suitable amino alcohol with an alkylsubstituted succinic acid to form an N(hydroxyalkyl) alkylsuccinimide, or with a suitable gamma keto acid (levulinic acid, for example) and reduce the product to form an N(hydroxyalkyl)- pyrrolidone-2. The compounds thus obtained are then. reacted. with lithium aluminumhydride in absoluteether to produce the-desired (I-pyrrolidyl) alkanols. Other (l-pyrrolidyl) allranols may be prepared by condensing a suitable pyrrolidine with a suitable aliphatic aldehydeto. give the desired (l-pyrrolidyl) alkanol. Certain of the (l-pyrrolidyl) alkanols referred to herein: and

methods for their preparation. are. described by:

Reid et al. in J. Am. Chem. Soc. '70, page 3100 (1949); by Moffett, in J. Org. Chem. 14,, 852. (1949); and in my copending application Serial? No. 773,522, filed September 11, 1947, now U. S. Patent 2,552,502, issued May 8, 1951.

The reaction of an acid chloride and a (l-pyrrolidyl) alkanol' to. form. an. ester ofthe-invention can: be carried. out. conveniently by mixing the two substances, together, either with; or.- with;- out the: addition of an inert. diluent such-as dry xylene or other hydrocarbon solvent. Reaction usually occurs at ordinary temperatures. and can beaccelerated and: carried substantially to completion'by'finally refluxing themixture for about thirty minutes: or longer. Upon allowing; the reaction mixture to coolgthe hydrochloride oil the basiozester generally crystallizes andcan' be separated from most of any inert diluent used. by filtration. The free ester. can be recovered and purified by dissolving the crude hydrochloride in water, extracting the solution with ether or other water-immiscible solvent to remove any remaining; inert diluent or.- other. water-insoluble sub.- stanne, and. finally alkalizing the solution with sodium carbonate or other alkali. The alkaline mixture is then extracted with ether or other suitable organic liquid and the extract eventually evaporated to drive off the solvent and recover the free basic esters. The free basic esters can be distilled at subatmospheric pressure to purify them, if greater purity'is desired.

Salts ofthe basic esters with hydrochloric; hydrobromic; hydriodic, sulmric, phosphoric, acetic, succinic; propionic, benzoic; citric, lactic, nitrobenzoic, picric, nitric,

p toluenesulfonic and" other acids, can be prepared readily byreacting the ester and the acid i'n-a: solvent suchas alcohol: or a mixture of. ethyl alcohol and ethyl acetate. Upon evaporation of the solvent, the salt remains as a residue, and

can be recrystallized from alcohol or other suitable organic liquid; a mixture of ethyl alcohol and ethyl acetate is particularly suitable for: recrystallization. Salts' with certain inorganic acids, especially with hydrochloric acid, are of particular value because of" their well-defined crystalline nature. Citric acid and other dibasic and tribasic acids combine with the basicesters in equimolecular proportions to form monoamino salts; whereas other dihasic and tribasic acids combine in accordance with their acid equivalences.

In addition to salts with acids, the basic esters of the present invention also form quaternary ammonium salts with alkyl halides. With methyl iodide, the methiodide salt is formed, and similar quaternary ammonium salts form with other alkyl halides. Representative compounds which can be used to form these. salts are, for example, benzyl chloride, ethyl bromide, methyl iodide, propyl bromide, ethyl chloride, allylbromide, etc.

with acids, such as 4 The quaternary ammonium salts prepared from the basic alkyl esters of the invention are generally well-defined crystalline compounds having sharp melting points, which are soluble to varying degrees in many organic solvents and are generally very soluble in water.

Although the preferred basic esters of; the invention are esters of disubstituted acetic acids (in which X of the general formula is hydrogen) iiiis to be understood that esters of other saturated alpha, alpha-disubstituted aliphatic acids, having either straight or branched carbon chains, are included: within the scope of the invention: Such' acids include alpha, alpha-disubstitutedv propionic, n-butyric, n-valeric, isoisobutylacetic, sec-butylacetic, tertebut'ylacetic, pelargonic and other aliphatic acids. Generally disubstituted products of aliphatic" acids having less than 10 carbon atoms in the molecule are preferred, but the invention is not to be-limitedin this respect.

As stated hereinbefore, one or two of the-substituents (Xand Z of the formula) on the alpha carbon atom of the aliphatic acid component of the esters of theinvention can be an alkyl radical, and at least one (Y of the formula)- of the substituents must be an aryl, aralkyl, cycloalkyl or cycloalkenyl radical. Alkyl radicals, present as one of'the substituents on-thealpha-carbon atom, can have either a straight or branched carbon chain and include methyl, ethyl, n-propyl; isopropyl, n-butyl, isobutyl', sec-butyl, hexyl, dodec'yl and manyothers. Generally speaking an alkyl radical containing not morethan 1-2 carbonatoms is preferred, although theinvention is not limited in this respect. Other substituent' radicals which can be present onthe alphacarbon atom of the acid component include, among many others, phenyl; naphthyl, o-tolyl, p-tolyl, xylyl, benzyl, methylbenzyl, diphenylmethyl, cycl'ohexyl', methylcyclohex-yl, propylcyclohexyl', cyclohexenyl', methylcyclohexenyl, cyclopentyl and cycl'opentenyl radicals;

The (l-pyrrolidylialkanol used in preparing theesters-of the invention can be a (l-pyrrolidyDethanol, a (l-pyrrolidyhpropanyl, or a (l-pyrrolidyDbutanol; The carbon chain of the group, -CnH2n-', can be either straight or branched. The pyrrolidinering can either be unsubstituted or it may contain up to 4-loweralkyl substituents on its carbon atoms. Representative lower-alkyl radical substituents are methyl, ethyl, propyl, isopropyl, butyl, tertiarybutyl, and other alkyl radicals having up to and including 6" carbon atoms. Representative (1- pyrrolidylialkanols which, among others, can be used in preparing esters of the invention include beta- (l-pyrrolidyl) ethanol, beta- (l-pyrrolidyl) buts-n01; betal-pyrrolidyl) isopropanol, beta (l pyrrolidyl) n propanol, alpha (1- pyrrolidyl) ethanol, alpha (l pyrrolidyl) isobutanol, beta (2 methyl 1 pyrrolidybethanol, gamma-(l-pyrrolldybpropanol, beta-(3- methyl-l-pyrrolidyl) propanol, gamma- (2,3-dimethyl l pyrrolidyl) butanol, alpha (2,5- dimethyl-i-pyrrolidyl) -n-butanol; beta-(2134imethyl-l-pyrrolidyl) butanol, and betal-pyrrolid'yl) isobutanol.

Although the preferred method for preparing the compounds of the invention comprisesreacting an alpha,alphadisubstituted. aliphatic acid chloride with. a (1-pyrrolidyl)alkanol, because of, the, high yield of pure .product obtained, it should bepointed out that they can also be prepared in. other conventional ways. Thus. an

valeric, n-caproic,

alkali-metal salt of an alpha,alpha-disubstituted aliphatic acid can be heated with a suitable (lpyrrolidyDalkyl halide, preferably in a solvent such as ethanol, isopropyl ether or butanol, and the desired ester isolated from the reaction product.

Free basic esters contemplated by the invention include, among many others, beta-(1- pyrrolidyDethyl alpha,alpha diphenylacetate, gamma (1 pyrrolidyDpropyl alpha,alpha diphenylacetate, beta (1 Dyrrolidyl) 1 methylethyl alpha,alpha-diphenylacetate, beta-(L pyrrolidyl) n propyl alpha,alpha diphenylacetate, betal-pyrrolidyl) ethyl alpha,alphadicyclohexylacetate, beta-(l-pyrrolidyl) ethyl a1- pha,alpha dicyclopentenylacetate, beta (1- pyrrolidyDethyl alpha,alpha dibenzylacetate, beta (1 pyrrolidyDethyl alpha phenyl alpha-cyclopentylacetate, gammal-pyrrolidyl) propyl alpha-phenyl-alpha-cyclopentylacetate, beta (1 pyrrolidyDisopropyl alpha-phenylalpha-cyclopentylacetate, betal-pyrrolidyl) -npropyl alpha-phenyl-alpha-cyclopentylacetate, beta (1 pyrrolidyDethyl alpha phenylalpha(delta-2-cyclopentenyl) -acetate, gamma- (1- pyrrolidyl) propyl alpha-phenyl-alpha- (delta-2- cyclopentenyl) acetate, beta (1 pyrrolidyDisopropyl alpha phenyl alpha (delta 2 cyclopentyl) acetate, beta- 1-pyrrolidyl) -n-propyl alpha phenyl alpha (delta 2 cyclopentenyl) acetate, gammal-pyrrolidyl) -n-butyl alpha phenyl alpha benzylpropionate, gamma(1 pyrrolidyDisobutyl alpha phenyl-alpha-cyclohexylbutyrate, beta- (1 -pyrrolidyl) isobutyl alpha-phenyl-alpha(delta-2-cyclohexenyl) acetate, alphal-pyrrolidyl) -n-propyl alphaphenyl alpha cyclohexylbutyrate, beta (2,3- dimethyl 1 pyrrolidyDethyl alpha butylbeta-cyclohexylvalerate, lbeta-( 2,4 dimethyl-lpyrrolidyl) -n-propyl acetate, delta (3,4 dimethyl 1 pyrrolidyl) n-butyl alpha methyl beta cyclopentenylacetate, alpha-(2-methyl-1-pyrrolidyl)ethyl alphabenzyl-beta-cyclohexylpropionate, and gamma- (2 methyl 1 pyrrolidyDpropyl alpha-benzyl-beta-cyclohexylpropionate.

Methods by which the compounds of the pres-' ent invention may be prepared are disclosed in the following Preparations and Examples, which are given by way to be construed as limiting.

PREPARATION 1. ETHYL ALPHA- l-PYRROLIDYL) PROPIONATE (CH 'CH'(NC4H )-'C0OCzHs) One hundred forty-eight grams (approximately 2.1 moles) of pyrrolidine was added porof 181 grams (approxi- (CHs CHBrCOOCzHs) benzene. A vigorous and 200 milliliters of dry exothermic reaction ocethyl alpha- (1 -pyrrolidyl) propionate, boiling at 84 degrees centigrade unalpha-ethyl-beta-phenylof illustration only and are not ture.

PREPARATION 2.BETA- 1-PYRROLIDYL)PROPANOL (CH HCH (NC H 'CH3) A mixture of 7.6 grams of lithium aluminum hydride and 250 milliliters of dry ether was prepared and 61.7 grams (approximately 0.36 mole) of ethyl alpha-(l-pyrrolidyDpropionate (prepared as described in Preparation 1) was added slowly to the mixture so as to cause gentle refluxing of the ether. The mixture was then allowed to stand for a few minutes without cooling and milliliters of water was added dropwise. The mixture was then cooled by adding ice and was acidified with hydrochloric acid. The aqueous layer was separated, Washed with ether and then rendered strongly alkaline with sodium hydroxide. The basic solution was then extracted repeatedly with ether and the ethereal extracts combined and dried with anhydrous potassium carbonate. The ether was then evaporated and the residual oil fractionally distilled. There was thus obtained 38.1 grams of beta-(1- pyrrolidyl)propanol, boiling at 80 degrees centigrade at a pressure of 11 millimeters of mercury absolute and having an index of refraction, (n

N. Found:

of 1.4758 and a density (d4 of 0.9733.

Analysis-Calculated: 10.84% N. Found: 10.96% N.

Neutral equivalent. Calculated: 10.84.

Found: 10.96.

PREPARATION 3.GAMMA 1-PYRROLIDYL)PROPANOL (CH-,0HCH-.-CH2NC4H pyrrolidine. The mixture was stirred vigorously and 100 grams (approximately 1.06 moles) of 3-chloropropanol-l was slowly added to the mix- The temperature of the mixture rose gradually and was maintained between about degrees Centigrade and about degrees centigrade during the addition. The mixture was then stirred for an additional thirty minutes and finally allowed to stand for several hours. Solid sodium hydroxide was then added until the mixture was saturated; the oily layer which formed was separated. The aqueous layer was extracted with benzene and the combined oily layer and benzene extract was fractionally distilled. A fraction was collected consisting of 55.5 grams of gamma-(l-pyrrolidyl) propanol, boiling at degrees centigrade under pressure of 43 millimeters of mercury absolute and having an index of refraction (11 of 1.4701.

PREPARATION 4.N- (Z-HYDRoxYErrHYL) -ALPHA- METHYLSUCCINIMIDE o oHaoH-(L NCHzOHzOH OH2C ll A mixture of 66 grams (approximately 0.5 mole) of methylsuccinic acid (pyrotartaric acid) and 73.4 grams (approximately 1.2 moles) of monoethanolamine was heated by means of an oil bath, the temperature of the mixture gradually rising to 260 degrees centigrade, until dismesa-:1 1

1. tillationooased: 'lfheresiduewas distilled under a reduced pressure: of. about one millimeter. of mercury absolute to obtaina viscous; oil. which, upon: fractionalvdistillation; yielded. 67.8 grams (86.4 per cent of the theoretical yield) of N(2. hydroxyethyl) alpha-methylsuccinimide, boiling at 102 degrees centi'gra'de at a pressure of'0;01 millimeter ofmercury absolute; and having an index of refraction: 2 )1 of 11495'0.

A.solution 051G218: grams (approximately GA mole) of N-(Z-hydroxyethyl) -alpha-methylsuccinimide (preparedasdescribed in Preparation 4) inzl'ommillilitersof dry ether was addedito a suspensionoft'iio grams or lithium aluminum hydride in"SBOmiillilitersof ether gentle. refluxing; of the ether. rhe mixture was then allowedto stand for a few minutes without cooling. and 2G milliliters of water was added dropwisi: The mixture was cooled to about ten degrees. centigradeby adding ice and thereafter was. acidified with aqueous hydrochloric. acid. The aqueouslayer was separated, washed with ether, and: made strongly alkaline with concentrated'. sodium: hydroxide. The basic solution was then extracted repeatedly with ether, the etherealextractscombined, dried withanhydrcus potassium carbonate; the'ether removed, and the residual oil fractionally distilled. There w. sthus obtained grams of 2- (S-methyl-l -pyrrolidyl) ethanol, distilling at 105 degrees Centigrade at a pressure of millimeters of mercury, and having a refractive index (115 of 1.4646.

PREPARATION 6.OTHER l-PYRROLIDYL ALKANOLS By procedures similar to those described in Preparations 4 and 5, the following l-pyrrolidyl alcohols were prepared:

(1) 2- (3,3 dimethyl-l-pyrrolidyl) ethanol boiling at 81 degrees centigrade at a pressure of 13' millimeters of mercury absolute, index of. refraction (Tl/ of 1.4580.

(2) 2- (BA-dimethyl-l-pyrrolidyl) ethanol boiling' at 88. degrees centigrade at pressure of l2:millirneters-of'mercury absolute, index of refraction (11. or 114594;

(3') 2-(2,3-dimethyl1-pyrrolidyl) ethanol (QHr-CHz-CH(CH3)--CH(CHi)N-CHr-CH:OH)

boiling at 86 degrees centigrade at a pressure of 13 millimeters of mercury absolute, index of refraction (nof 1.4661.

(4) 3- (Z-methyl-l-pyrrolidyl) propanol-l boiling at IO'Ode'grees c'entigrade at a pressure of 18 millimeters of mercury absolute, index of refraction (11, of 1.4672.

The preparation of other l-pyrrolidyl allianols is described hereinafter.

PREPARATION 7.-1- (2-HYoRoxYET1-1YL) -5-METHYL- at a rate such as to cause Approximately 0.2. gram! ot platinum. oxide catalyst in suspensionin25 milliliterswof -absolute ethanol was reduced to platinum, a solution.- of 34.8 grams (approximately'0;3 -mole-) oilevulinic acid (CHsCO(CH2)'zCOOH) and 37.8 grams (approximately O.62 mole) of ethanolaminein. '75 milliliters ofv absolute alcohol wasadded, and the mixture was hydrogenated atabout 50. pounds pressure-and. room. temperature for about. four hours, after whichtime thez-theoreticaL amount of hydrogen had been absorbed: After. removingthe catalyst and solvent,.the:residue-wasfraetionally distilled. There wasthus obtained. 42.5 grams per cent of the theoretical yield) of 1 (2 -hydrc::yethyl)--5-methylpyrrolidone -2, boiling at 167 degrees centigrade. ata pressure of 12 millimeters of mercury absolute, and having an index ofrefraetion (12 of 13 883. Bachm'an and Mayhen, J Org. Chem. 10, 243- (1945 alkyla'ted 5-methylpyrrolidone-2 with ethylene chlorohydrin and obtained a product having, somewhat different physical. constants.

A mixture of 223.5 grams (approximately-3.1 moles) of methyl" ethyl ketone; 183:3 grams-of ethanolamine (approximately 310 moles) and 500 milliliters of benzene wereheated in areaction flask equipped with a distillation. condenser. The' collected distillate was separated into two layers, the organic layer or which was returned to the reaction" flask; This procedure was continued until no more water collected in the distillate. After removing: the benzene by distillation, 232.9 grams (67.3 percent. of the theoretical'yield) of.2 methyl 2 ethyloxazolidine was obtained.

PREPARATION 10.N-2-ETHANOL-N- (LnErHrL-l- ETHYL-3BUTENYL) AMINE Allylmagnesium bromide was prepared byreacting 242 grams (approximately 2.0 moles) of allyl bromide with 145.8 grams (approximately 6.0 moles) of magnesium in 1500' milliliters of ether. The mixture was distilled to remove one liter of ether, and one liter of tetrahydrofumn was thereafter added. 2 methyl 2' ethyloxazolidine (approximately 0.9 moleprepared as described in Preparation 9) in 200' milliliters" of anhydrous ether was added dropwise to the-allylmagnesium bromide over" a period of about two hours. After the addition of: the oxa'zolidine' was completed, one liter of the solvent was removed by distillation and the residueallowed to stand overnight. Thereafter, approximately400 milliliters of water was added to-the mixture andthe resulting. mass filtered. The nitrate was continuously extracted with ether for about five hours. The ether extract was separated, acidified with aqueous hydrochloric acid, adjusted to a pH of 9.0 with aqueous sodium hydroxide, and the oily precipitate which formed was extracted with one 100-milliliter portion and three 25-milliliter portions of ether. The ether extracts were combined, dried over anhydrous potassium carbonate, the ether removed and the residue distilled at a reduced pressure of about 16 millimeters of mercury absolute. There was thus obtained 55.6 grams (35.3 percent of the theoretical yield) of N 2 ethanol N (1 methyl 1 ethyl 3 butenyl) amine, boiling at 113.5 degrees centigrade at 16 millimeters of pressure absolute. Its refractive index (11 was 1.470.

Analysis. Calculated: 3.91% N. Found: 8.83% N.

PREPARATION 11.-2- 2-METHYL-2-mHYL-1- PYRROLIDYL) ETHANOL A mixture of 33.6 grams (0.21 mole) of bromine in 100 milliliters of chloroform was added to 32.5 grams (0.21 mole) of N 2 ethanol N (1 methyl 1 ethyl 3 butenyl) amine (described in Preparation in 100 milliliters of chloroform at a temperature below about forty degrees centigrade. The chloroform was reand the resulting organic 40 degrees oentigrade.

PREPARATION 12.,B,'y-DIMETHYL-'y-NITROVALERIG AoID (CHr-C(CH3)(N02) CH('cH3)-CH2-C0OH) A mixture of 238.6 grams of 2,3 dimethyl 3 nitrovaleronitrile (Buckley, Elliott, Hunt and Lowe, J. Chem. Soc. (London) 1947, 1505) and 8.91% N. Found:

drochloric acid to a pH of about 2.5, with one 250-milliliter portion of ether, and three 100-milliliter portions of ether, the extracts combined, dried over potassium carbonate, and the ether removed.

grees centigrade at a pressure of 0.05 millimeter of mercury absolute. This material, when recrystallized from carbon tetrachloride and hexane, melted at 815-82 degrees centigrade.

Analysis.-

Neutral PREPARATION 13.4,5,5-TR1METHYLPYBRoLIDoNE-2 A mixture of 57.6 grams of fiw-dimethyl-vnitrovaleric acid (prepared as described in Preparation 12), 250 milliliters of absolute ethanol,

grams of Raney nickel was placed in PREPARATION 14.-2,2,3mmmnrnnrnnomnmn A mixture of 4,5,5-trimethylpyrrolidone-2 (9.5 grams or approximately 0.5 mole) in milliliters of tetrahydrofuran was added dropwise to 9.5 grams (approximately 0.25 mole) of lithium alumimnn hydride in 200 milliliters of tetrahydrofuran maintained at reflux temperature. The mixture was thereafter refluxed for five hours and allowed to cool and left standing for sixteen hours. Approximately 500 milliliters of water and fifteen milliliters of concentrated hy- The tetrahydrofuran was removed by distillation, the mixture washed with fifty milliliters of ether, made basic to a pH of 9.0 with aqueous sodium hydroxide, and thereafter distilled with steam. The distillate was saturated with potassium carbonate and extracted with one 250-milliliter and three 100-milliliter portions of ether. The ether 11.01% N. Found:

was 1.4400.

Analysis-Calculated: 12.08%; 11.93% N.

PREPARATION 15.2- 2,2,3-TRIMETHYL-l-PYRROLIDYL) ETHANOL A mixture of 13.8 grams (approximately 0.12 mole) of 2,2,3-trimethylpyrrolidine and 9.8 grams (approximately 0.12 mole) of ethylene heated at degrees centigrade for about two hours. The reaction mix- 12.38% N. Found:

,of lithium aluminum hydride.

,of mercury,

ture was shaken with 25 milliliters of fifty percent sodium hydroxide and thereafter extracted with one IOO-milliliter and two fifty-milliliter portions of ether. The extracts werecombined, dried over anhydrous potassium carbonate, and the ether removed by evaporation. On distillation of the residue there was obtained 13.6 grams (72.3 percent of the theoretical yield) of 2-(2,2,3- trimethyl-l-pyrrolidyl) ethanol having a boiling point of 98.5 degrees centigrade at a pressure of fifteen millimeters of mercury absolute; its

refractive index (n was 1.4666 and its density (D4 was 0.93316.

Analysis-Calculated: 9.23%; 9.38% N.

PREPARATION 16.-ETHYL ALPHA- (2,2-DIMETHYL-1- rrsrorrnyr) rxorronxra (Oni.CHr0.ooH cr1o-Nc oHorOHronrom) 8.91% N. Found:

In a manner similar to that described in Preparation 1, 90.6 grams (approximately 0.5 mole) of ethyl alpha-bromopropionate was reacted with 44.8 grams (approximately 0.45 mole) of 2,2-dimethylpyrrolidine. There was thus obtained 38.3 grams (48 percent of the theoretical yield) of ethyl alpha:(2,2:dimethylpyrrolidyl)- propionate, having a boiling point of 99-101 degrees centigrade at thirteen millimeters of mercury absolute, and a refractive index (n fi) of PREPARATION 17.-2-(22-01mmHYL-I-PYRROLIDYL) PBOPANOL In a manner similar tothat of Preparation 2, 38.3 grams (approximately 0.192 mole) of ethyl alpha (2,2 dimethyl 1 .-.pyrrolidyl) propionate (prepared as described in Preparation 16) was reacted with 7.6.grams (approximately 0.2 mole) There was thus obtained 12.7 grams (40.2 percent of the theo- .retical yield) of 2.-(2,2dimethyhhpyrrolidyl)- boiling point of 94 degrees centigrade at a pressureof sixteen millimeters a refractive index M 2 of 1.4582, anda density (D4 of 0.9187.

Analysiarcalculatedt ;8.91% N; M 45.5. Found: 8.85%; 9.06% N; M 47.0.

Forty-two and iouretenths grams (approximately 02 mole) of diphenylacetieacid was-heated at reflux temperature with 71.4 grams (approximately 0.6 mole) of thionyl chloride .fora period of one hour. The excess thionyl chloride was remov d first b a u .m s illatio n a steam bath, and thereafter three fifty-milliliter portions of dry benzene were added and the henzene wasdistilled out after each addition. Qne

hundred milliliters of dry xylene was addedto the resulting cooled diphenylacetyl chloride, followed by 23.0 grams (approximately 0.2 mole) of beta- (l-pyrrolidyl) ethanol in 50 milliliters of xylene. The reaction mixture, which separated rapidly into two layers, was refluxed .for onerhalf hour and he a ow d o t n o er t in a serator.

The xylene was then decanted from the solid lower layer. The solid was dissolved into 250 milliliters of water, the cloudy solution exand tracted with ether. The extracted solution was coholic hydrogen centigrade, and

solvents. Analysis of betal-pyrrolidyl) ethyl diphenylacetate hydrochloride:

Calculated 09. 45 6. 99 4. 05 10.25 Found"; 69.73 6.72 4.35 10.11

Example 2.Beta- (-1-pyrrolidyl) ethyl alphaphenyl-alpha- (delta-Z-cyclopentenyl) acetate (mar-Carolus)-coo+cn -or nc.a

Thirty-five and one-tenth grams (approximately 0.174 mole) of ,alpha-phenylfalnha- (delta-Z-cyclopentenyl) acetic acid, obtained from phenyl malonic ester and delta-.2-.cycl opentenyl chloride and melting at 71 degrees centigrade, was treated-with thionyl chloride to-form the acid chloride as described irrExample 1. One hundred grams of xylene was .added, the solution ,was cooled to about 10 degrees centig-rade, and a solution of 20 grams (approximately 0.174 mole) of beta-(l-pyrrolidyl) ethanol in 50 milliliters of xylene was added. The mixture was allowed to stand at room temperature for fifteen minutes and then heated at refiuxfor one-half hour. The mixture was cooled to room temperature, agitated thoroughly with 300 milliliters of water, and the xylen layer separatedand discarded. After extracting twice with ether, the aqueous layer was alkalized with aqueous sodium carbonate and extracted several times with o her. Theextracts from the alkaline solution were combined, dried. and the ether evaporated, and the residue distilled in vacuo. There was thus obtained beta- (l-pyrrolidyl) ethyl alpha-.phenylealpha- (delta- 2-cyclopentenyllacetate, boiling at -150 degrees centigrade at 0.04 millimeter of mercury pressure absolute. Analysis of beta-(lepyrrolidyl) ethyl alpha phenyl :alpha-(delta-2-cyclopentenyl) acetate:

Calculated.. 76.22 8.42 4.68 Found ;L. 76. 55 7. 79 4.68

The yd o hmridepre ar d in ac o an e. t the g ne a o edur d s r ed in E a ple and c ys al ize om th acet te. melted a Calculated Found. 68.06

Alpha phenyl alpha (delta 2 cyclopentenyDacetyl chloride, prepared as described above, is a liquid having a boiling point of 78 degrees centigrade at a pressure of 0.1 millimeter of mercury and an index of refraction (11 of 1.5430.

Analysis. Calculated: 15.02% C1.

The monocitrate of beta-( 1-pyrrolidyl) ethyl alpha phenyl alpha (delta 2 cyclopentenyl)acetate was prepared as follows:

Approximately one molecular proportion of citric acid was dissolved in a hot mixture of ethyl acetate and methanol and the solution added to a hot solution of approximately one molecular proportion of distilled beta-(l-pyrrolidyl)ethyl alpha phenyl alpha (delta 2 cyclopentenyl)acetate in ethyl acetate. The clear solution was allowed to cool, whereupon mono-(beta-(lpyrrolidyl) ethyl alpha phenyl alpha (delta 2-cyclopentenyl)acetate) citrate separated in good yield in the form of crystals melting at 955-97 degrees centigrade.

AnayZsis.-Calculated: 2.85% N. Found: 2.36%

16.07% Cl. Found:

Ex mple 3.-Quatemary ammonium salts of beta- (1 -pyrrolz'clyl) -ethyl alpha-phenyZ-alpha- (delta-Z-cyclopentenyl) acetate.

The following quaternary ammonia-m salts ct beta (1 pyrrolidyl) ethyl alpha phenyl alpha-(delta-2-cyclopentenyl) acetate (Example were prepared by reaction of the ester with the appropriate alkyl halide. Their melting points were found to be as specified:

Meltingv point,

degrees centigrade Methobromide 1035-1055 Methiodide 112.5-114.5 Ethobromide 1 129 -l.3l Ethiodide 127.5-129 Allyl bromide 117 -119 Example 4.Beta-(1-pyrrolidyl) ethyl alpha phenyZ-alpha-cyclopentylacetate I C H N Calculated 75. 71 4. 64 Found 74. 4.

The hydrochloride, prepared as in Example 1 and crystallized from ethyl acetate, melted at 101-102 degrees centigrade.

Analysis of beta-(pyrrolidyl-Dethyl alphaphenyl-alpha-cyclopentylacetate hydrochloride:

I G I H Calculated 67. 54 8. 35 4. 14 10. 50 Found 67. 12 8. 12 4. 36 10. 61

Example 5.2 (2 methyl 1 pyrrolidyl) ethyl a-pheayZ-a- (deZta-Z-cycloheaenyl) acetate cyclohexenyl) acetic acid (Kollofi', ruiT and Moflfett, J. Am. Chem. Soc. 70, 3862 (1948)) and 73 milliliters of thionyl chloride was heated on a steam bath for one hour. After removal of the solvent, the residue was distilled through a short fractionating column whereupon 111 grams of l-phenyl-l-(delta-Z-cyclohexenyl) acetyl chloride was obtained, distilling at 97 degrees centigrade at a pressure of 0.04 millimeter of mercury absolute and having an index of refraction (11, of 1.5478.

To a solution of 11.8 grams of the thus prepared acid chloride in 10 milliliters of dry benzene was added rapidly a solution of 7.75 grams of 2- (2-methyl-1-pyrrolidyl) -ethanol in 15 milliliters of dry benzene. After the initial reaction had subsided, the mixture was heated under reflux for an additional two hours, cooled, and shaken with ice water, ether, and 10 milliliters of hydrochloric acid. The aqueous layer .was separated, extracted once with ether, and then made basic with cold sodium hydroxide solution. The insoluble product which separated was extracted with ether, the ether solution washed twice with water and once with saturated sodium chloride solution, dried, the solvent removed, and the residue fractionally distilled under a reduced pressure of less than 1 millimeter of mercury. There was thus obtained 14.8 grams of 2 (2 methyl 1 pyrrolidyl) ethyl a phenyl a (delta 2 cyclohexenyl) acetate, distilling at 134 degrees centigrade at a pressure of 0.03 millimeter of mercury absolute, and having an index of refraction (11 of 1.5248.

Analysis.-Calculated for C21H29NO2Z 4.28% N. Found: 4.20% N.

A slight excess of dry hydrogen chloride was passed into a solution of 14.3 grams of the above base in absolute ether. 2-(2-methyl-1-pyrrolidyl) ethyl a-phenyl a (delta-2-cyclohexenyl) acetate hydrochloride separated at once as an oil which solidified, and, after crystallization from methyl ethyl ketone, had a melting point of 146-148 degrees centigrade. Analysis-Calculated for 9.74%. Found: 01, 9.54%.

OTHER l-PYRROLIDYL ESTERS In a manner similar to that described in the foregoing examples, the following basic l-pyrrolidyl esters and their salts were prepared by reaction of the appropriate (l-pyrrolidyDalkanol and substituted acetic acid:

6. 2-(Z-methyl-I-pyrrolidyl) ethyl a-phenyl-a- (delta-2-cyclopentenyl) acetate I boiling point 150 degrees centigrade at a pressure of 0.2 millimeter of mercury; 12 1.5197. Hydrochloride, melting point 126-1285 degrees centigrade after crystallization from ethyl acetate.

momma boiling point 125 degrees .centigradeiat a ,pressure of 0.02 millimeter of mercury; .1L 5,I1.5130. Hydrochloride, melting point 133-136 degrees centigrade after crystallization iroxn a mixture of methyl ethyl .ketone and ethyl acetate.

8. 2-(2-methyl-l-pyrrolidyl) ethyl a-cyclopen- 'tyl-upropyl acetate .(mm-crucinn-ooo-cHTcHTN-cHLCH -GHz-QHrQHi) Ldff boiling 'point 159 degrees centigrade at a'pressure of02millimeter "of mercury; 11, 1.4672. 'Hydrochloride, melting point 1195-1 2055 degrees centig-rade after crystallization from a mixture or ethyl acetate and ether.

9. '2-(2-methyl-l-pyrrolidyllethyl (delta-2-cyclopentenyl)acetate crnq-cmcirm-c 0 o-cur'cm-n-c H( o rm-dnz-c H2 0 H2) a-butyl-a- Zboilmg1point103 degreescentigraderat axpressure of .0i02tmillimeter 'of mercury; 1.4735. Hy- :drochloride,*meltingpoint 98.5-1'00 degrees centigmdeatter crystallization from: an ethyl acetatezetherzimixture.

10. 12(Z-methyi-l-pyrrolidyl)ethyl u.-='(delta-'2- myclohexenyl) a-'(delta-2-cyclopentenyl) acetate boiling point 180 degrees centlgrade at'a pressure 10! 0.02 millimeter -.of mercury; c 1.5.022. .Hy-

boiling point .121 degrees 'centigrade at .a pressure of 0.01 millimeter 'of mercury; 11 5 1.5238. .Hydrochloride, melting point 102-106 degrees centigrade after crystallization from an ethyl acetateetner mixture.

14. 2- (3-methyl-1-pyrrolidyl) ethyl a-pheny'lm- ('delta-2-cyclohexenyl) acetate (cfim-(JHwiHd-eo Q-CEZ-OHQ-N-CHTGH 0219-0111-0112) boiling point 133 degrees centigrade at'a pressure of 0.01 millimeter of mercury; 1.5238. Hydrochloride, melting point -123 degrees centigrade after crystallization roman ethyl acetateether mixture.

'15. 2-(3-methyl-1-pyrrolidyl) ethyl a-propyl-acyclopentyl'acetate (C5HoGH(C H1)-O0O-CHz-CHz-N-CHg-OH(GHQ-CHz-CH boiling point 87 degrees centigradeat a pressure of 0.01'millimeter or'mercury; n 1.4660. .Hydrochloride, melting point 96.5-98 'degrees centlgrade after crystallization from an ethyl acetateether mixture.

16. 2- (3-methyl-l-pyrr0lidyl) ethyl a-(delta-Z- cyclopentenyl) a. (delta 2 cyclohexenyD- acetate boiling point 126 degrees centigrade:at:a pressm'e of 0.01 millimeter of mercury; 11 115012. Hydrochloride, :melting point 99-100 after crystallization from an ethyl acetate-ether :mixture.

1']. 2- (12,5 dimethyl 1 pyrrolidyl) ethyl aphenyl-adelta-2-cyclopentenyl) acetate drochloridemelting point 107-1110 degrees centigrade after crystallization from ethyl acetate.

11. B-.(2 methyl-lepyrrolidyl)propyl a-zphenylmtdelta-zz -eyclopentenyl) acetate boiling point, 131 degrees centigrade a't a'pressure -of 0.02 millimeter of mercury; n 1.5153. Hydrochloride, .melting point 1-1'7.5-122.5 after crystallization fromethyl acetate.

boiling point 132 degrees centigrade-at a pressure .0! 0.01 millimeter .of mercury; 11 1.5169. Hy-

18. 2- (2,5 dimethyl- 1 -'pyrrolidyl)ethyl nphenyl-m-cylopentylacetate drochloride, meltingpcint 166-1167 degrees centigrade after crystallization from vanethyl acetate- .ether mixture.

12. 3-'(2-methyl1 pyrrolidyllpr0pyl .a-propyl- -.cyclopentylacetate boiling point 138 degrees centigrade at a, pressure of 0.06 millimeter of mercury; 'n 1.5089. Hydrochloride, melting point 1355-1365 degrees centigrade after crystallization from methyl ethyl ketone.

boilingpoint 117 degrees centigrade at a pressure of 0.03 millimeter of mercury; n 1.4674. Hy-

19.12 -.(2,5 -;dimethy1 1 pyrrolidyl) ethyl nphenyl-a- (delta-.2 -.cyclohexenyl) acetate drochloride, melting-point '167-169 degrees centigrade after crystallization from an ethyl acetateether mixture.

13. 2-.(3-methyl-'lpyrrolidyl).ethyl u-phenyla- ('delta-2-cyclopentenyl) acetate elm-cH(0.115)coo-cm-om-rr-cm-crt camera-$112) boiling point degrees 'centigrade at :a, pressure of 0.03 millimeter of mercury; 11. 1.5202. Hydrochloride, melting point 123-128 degrees centigradeafter crystallization from a smixturelof methyl ethyl ketone and ethyl acetate.

20. .2- (2,5-dimethyl-l-pyrrolidyl) ethyl a-cyclopentyl-a-propylacetate boiling point 113 degrees centigrade at a pres- 26. 2 (2,3 dimethyl 1 pyrrolidyDethyl asure of 0.07 millimeter of mercury; n 1.4657. cyclopentyl-a-propylacetate Hydrochloride, melting point 116-120 degrees boiling point 109 degrees centigrade at a prescentigrade after crystallization from ethyl acesure of 0.03 millimeter of mercury; 11 1.4670.

tate. Hydrochloride, melting point 101-104 degrees 21. 1-(2,5-dimethyl-1-pyrrolidyl)propyl-2 acentigrade after crystallization from an ethyl phenyl-a-(delta-2-cyclopentenyl) acetate acetate-ether mixture.

boiling point 124 degrees centigrade at a pres- 27. 2 (2,4 dimethyl 1 pyrrolidybethyl asure of 0.015 millimeter of mercury; n 1.5097. phenyl-a-(delta-2-cyclopentenyl) acetate Hydrochloride, melting point 143-146 degrees boiling point 132 degrees centigrade at a prescentigrade after crystallization from ethyl acesure of 0.02 millimeter of mercury; n 1.5147. tate. Hydrochloride, melting point 150-152 degrees 22. 1 (2,5 dimethyl 1 pyrrolidyDpropylcentigrade after crystallization from methyl ethyl 2 a-phenyl-a- (delta-Z-cyclohexenyl) acetate ketone.

boiling point 154 degrees centigrade at a pres- 28. 1 (2,4 dimethyl 1 pyrrolidyDpropylsure of 0.05 millimeter of mercury; n 1.5147. 2 a-phenyl-a-(delta-Z-cyclopentenyl)acetate (C H1OH(C6H5)-OOOCH(CHa)OHzN-CH(OHs)CHz-OH(CH3)OH;) 23. 1-(2,5-dimethyl-l-pyrrolidyl)propyl-2 aboiling point 121 degrees centigrade at a prescyclopentyl-a-propylacetate sure of 0.015 millimeter of mercury; n 1.5078.

boiling point 117 degrees centigrade at a pres- Hydrochloride, meltin point 136-140 degrees sure of 0.03 millimeter of mercury; 12 1.4636. centigrade after crystallization from a mixture 24. 2 (2,3 dimethyl 1 pyrrolidyl) ethyl aof ether and ethyl acetate.

DhBIIYI-a- (delta-2-cyclopentenyl) acetate (CtH1OH(OaH )COOCHaCHz-NCH(CH:,)CH(OH )CHTCH;)

boiling point 138 degrees centigrade at a pressure of 0.03 millimeter of mercury; n 1.5170. 29. 2 (3,4 dimethyl 1 pyrrolidyDethyl a- Hydrochloride, melting point 105-1075 degrees phenyl-a-(delta-2-cyclopentenyl)acetate centigrade after crystallization from an ethyl acetate-ether mixture. boiling point 126 degrees centigrade at a pres- 25. 2 (2,3 dimethyl 1 pyrroldiyhethyl asure of 0.015 millimeter of mercury; n 1.5133.-

phenyl-a- (delta-2-cyclohexenyl) acetate boiling point 151 degrees centigrade at a pres- Sure of 0.04 millimeter of mercury; n 1.5219. 30. 2 (3,4 dimethyl l pyrrolidyDethyl a- Hydrochloride, melting point 145-156 degrees phenyl-a-cyclopentylacetate centigrade after crystallization from methyl boiling point 125 degrees centigrade at a pressure ethyl ketone. of 0.01 millimeter of mercury; 11 1.5065.

19 -31. 2 (3,4 dimethyl- 1 pyrrolidyl) ethyl phenyl-e- (delta-2-cyclohexenyD-acetate The melting point 0f the hydrochloride 1195-121 degrees centigrade.

boiling point 142 degrees centigrade at a pressure 0110.02 millimeter of mercury; n 1.5180. Hydrochloride, melting point 122.5-124 degrees oentigrade after crystallization :from ethylacetate. 32. 2 (2 methyl 2-ethyl-1-pyrrolidyl) ethyl a-cyclopentyl-a-n-propylacetate The methochloride has a melting point of 1805-1815 .degrees centigrade; analysis: calculated 10.28% Cl; found 10.00% Cl. V

The methobromide has a. melting point 0! 206-209 degrees centigrade.

boiling point degrees centigrade at 0.06 millimeter of mercury absolute; n 1.4675. Hydrochloride, melting point 148-150 degrees centigrade; analysis: calculated 10.20% Cl; found 10.17%, 10.23% Cl.

33. 2 (methyl 2-ethyl 1 pyrrolidyl) ethyl n. (delta-2-cyclopentenyl) -a-phenylacetate The melting point of the ethobromide is 149.5- degrees centigrade.

38. 2 '(1 vpyrrolidyl) ethyl a. phenyl a cyclohexylacetate '(COH11-CH(C6H5)C o o-cm-orh-n-cm-om-onr-cm) boiling point 143-144 degrees Centigrade at 0.03 millimeter of mercury absolute; 15 1.5069. Hydrochloride, melting point -167 degrees centigrade; analysis: calculated 9.35% Cl; found 9.40%, 9.37% Cl.

34. 2 (2,2,3 trimethyl-l-pyrrolidyl)ethyl cyclopentyl-a-n-propylacetate boiling point 104-105 degrees centigrade at 0.06 millimeter of mercury; 11 1.4690. Hydrochloride, melting point 153-154 degrees Centigrade; analysis: calculated 10.34% Cl; found 10.25%, 10.04% Cl.

35. 2 (2,2,3 trimethyl 1 pyrrolidybethyl a- (delta-2-cyclopentenyl) -a-phenylacetate boiling point 125 degrees centigrade at 0.06 millimeter; 11 1:5204; analysis: calculated 4.44% N; found 4.46% N. Hydrochloride, melting point 129-130 degrees centigrade; analysis-z calculated 10.08% 01; found 9.95% Cl.

39. 3 (1 pyrrolidyl) propyl a. phenyl a. cyclohexylacetate boiling point'145 degrees'centigrade at 0.06 millimeter; 11 1.5177; analysis: calculated 4.25% N;

boiling point 142-143 degrees Centigrade at 0.05 millimeter of mercury absolute; 11. 1.5160. Hydrochloride, melting point 120-132 degrees centigrade; analysis: calculated 9.35% 01, found 9.29%, 9.41% Cl.

36. 2 (2,2 dimethyl 1 pyrro'lidy'lmropyl cyclopentyl-a-n-propylacetate found 4.16% N. Hydrochloride, melting point 123-1245 degrees centigrade; analysis: calculated 9.69% Cl; found 9.60% C1.

40. 2 (1 pyrro'lidyD-ethyl a phenyl u.- delta-2-cyolohexenyl) acetate boiling point 137 degrees centigrade at 0.07 millimeter; n 1.5295; analysis: calculated 4.47% N;

boiling point 117.5-119 degrees centigrade at 0.07 millimeter of mercury, n 1.4688. Hydrochloride, melting point 108.5-110 degrees centigrade; analysis: calculated 10.25% Cl; found 10.18%,

37. 2 (2,2 dimethyl 1 pyrrolidyl) ethyl 0.-

the boiling point of the ester is 100 degrees centigrade at a pressure of 0.03 millimeter and its refractive index (11 1.4679.

found 4.61% N. Hydrochloride. melting point 132-134 degrees centigrade; analysis: calculated 10.13% Cl; found 10.08% Cl.

Methobromide, melting point 127-129 degrees centigrade.

Ethobromide, melting point 136-138 degrees centigrade.

41. 3-(1-py1rolidyl) propyl a-phenyl-a- (delta- 2-cyclohexenyl) -acetate boiling point 139 degrees centigrade at 0.07 millimeter; n 1.5260; analysis: calculated 4.28% N; found 4.41% N. Hydrochloride, melting point 129-133 degrees centigrade; analysis: calculated 9.74% CI; found 9.83% CI.

42. 2- (1 -pyrrolidyl) -1-methylethyl a- (delta-2-cyclohexenyl) acetate a-phenylboiling point 112 degrees centigrade at 0.03 milboiling point 120 degrees centigrade at 0.03 millimeter; 11 1.5219; analysis: calculated 4.28% N; found 4.33% N. Hydrochloride, melting point 177-186 degrees centigrade; analysis: calculated 9.74% Cl; found 9.48% Cl.

43. 3-(1-pyrrolidyl)propyl a,a diphenylacetate boiling point 143 degrees centigrade at 0.01 millimeter; n 1.5492; analysis: calculated 4.33% N; found 4.36% N. Hydrochloride, melting point 1425-1435 degrees centigrade; analysis: calculated 9.85% Cl; found 9.75% Cl.

44. 2 (l-pyrrolidyl)-1-methlyethyl a,a-diphenylacetate boiling point 119 degrees centigrade at 0.01 millimeter; n 1.5455; analysis: calculated 4.33%

N; found 4.45% N. Hydrochloride, melting point 166-167 degrees centigrade; analysis: calculated 9.85% Cl; found 9.72% Cl.

45. 2- (1-pyrrolidyl)propyl a,a-diphenylacetate boiling point 146 degrees centigrade at 0.01 millimeter; n 1.5493; analysis: calculated 4.33% N; found 4.26% N. Hydrochloride, melting point 117.5-120 degrees centigrade; analysis: calculated 9.85% Cl; found 9.81% 01.

46. 2- (l-pyrrolidyl) ethyl a-Il-DIODYl-a- (delta-2-cyclopentenylacetate boiling point degrees centigrade at 0.03 millimeter; n 1.4761; analysis: calculated 5.28% N; found 5.40% N. Hydrochloride, melting point 67-71 degrees centigrade; analysis: calculated 11.74% Cl; found 11.65% Cl.

47. 3- l-pyrrolidyl) propyl a-n-propyl-a- (delta-Z-cyclopentenyl) acetate (C H -CH C3H7) -C0 OCH CH CH NC H boiling point 120 degrees centigrade at 0.05 millimeter; n 1.4758; analysis: calculated 5.01% N; found 5.10% N. Hydrochloride, melting point 83-85 degrees centigrade; analysis: calculated 11.23% Cl; found 11.02% Cl.

48. 2- l-pyrrolidyl) -1-methylethyl PYI-a- (delta-Z-cyclopentenyl) acetate ('CsHv-CH (C3111) COO'CH (CH )-CHZNC H boiling point degrees centigrade at 0.025 millimeter; 12 1.4719; analysis: calculated 5.01% N; found 4.87% N. Hydrochloride, melting point 97-99 degrees centigrade; analysis: calculated 11.23% Cl; found 11.16% Cl.

49. 3- (1-pyrrolidyl) propyl a-PhBIlYl-a-CYCIO- pentylacetate (C H9-CH (CH3) CO OCH -;CHZCH2NC4HS) boiling point 125 degrees centigrade at 0.03 millimeter; 12 1.5146; analysis: calculated 4.44%

a-n-prolimeter; n 1.5103; analysis: calculated 4.44% N; found .42% N. Hydrochloride, melting point -125 degrees centigrade; analysis: calculated 10.11% Cl; found 10.02% Cl.

51. 3-(1-pyrrolidyl)propyl aphenyl-a.-(delta- 2-cyclopentenyl) acetate boiling point 129 degrees centigrade at 0.04 millimeter; n 1.5220; analysis: calculated 4.47% N; found 4.61% N. Hydrochloride, melting point 117-120 degrees centigrade; analysis: calculated 10.13% Cl; found 10.04 Cl.

52. 2-(l-pyrrolidyl) -1-methylethyl a- (delta-Z-cyclopentenyl) acetate 05117-013 ('CaHg )COO-'CH (CH -CH NC H boiling point 119 degrees centigrade at 0.05 millimeter; n 1.5175; analysis: calculated 4.47% N; found 4.61% N. Hydrochloride, melting point 184-187 degrees centigrade; analysis: calculated 10.13% C1; found 10.04% C1.

53. 2 (l-pyrrolidyDethyl a (delta-2-cyclopentenyl) -a- (delta-Z-cyclohexenyl) acetate boiling point 110 degrees centigrade at 0.01 millimeter; w 1.5064; analysis; calculated 4.62% N found 4.77% N. Hydrochloride, melting point 1055-1065 degrees centigrade; analysis: calculated 10.43% Cl; found 10.45% Cl.

54. 3-(l-pyrrolidyl)propyl a (delta-2-cyclopentenyl) -a- (delta-Z-cyclohexenyl) acetate oungomosm)-co0-cH2oHz-cH2-No.H boiling point 124 degrees centigrade at 0.01 millimeter; 11. 1.5043; analysis: calculated 4.41% N; found 4.36% N. Citrate, melting point 120.5-122 degrees centigrade.

55. 2- (l-pyrrolidyl) -1-methylethyl a- (delta- 2-cyclopentenyl) a- (delta 2-cyclohexenyl) acetate (CqHg'CH (c5117) CO 0-CH (CH8) -4CH2-N'C4H8) boiling point 125 degrees centigrade at 0.03 millimeter; n 1.5008; analysis: calculated 4.41% N; found 4.47% N. Hydrochloride, melting point 147-158 degrees centigrade (dec); analysis: calculated 10.02% Cl; found 10.07% Cl.

56. 2- l-pyrrolidyl) -n-propyl a-(delta-2-cyclopentenyl) -a- (delta-Z-cyclohexenyl) acetate boiling point 114 degrees centigrade at 0.01 millimeter; n 1.5065 analysis: calculated 4.41% N; found 4.46% N. Citrate, melting point 127-129 degrees centigrade.

57. 2 (l-pyrrolidyDethyl a-n-propyl-a-cyclopentylacetate boiling point 95 degrees centigrade at 0.01 millimeter; n 1.4686. Hydrochloride, melting point 102-104 degrees centigrade.

58. 3- l -pyrrolidyl) propyl a-Il-DI'ODYl-a-CYCIO- pentylacetate a-phenylboiling point 10,11degrees centigrade at 0.01 millimetern 1.4690 -Hydrochloride, melting point 115.5-116;5 degrees centigrade; analysis: calculated:11.55% Clyiound 11.30% Cl.

59. 2-(1-pyrrolidyl) -1-methylethyl (rm-propyla-cyclopentylacetate boiling point 87 degrees centigrade at 0.008 millimeter; n 1.4648. Hydrochloride, melting point 107 -109wdegrees centigrade.

60. 2-(1-pyrrolidyl) ethyl pentylacetate a-n-butyl a-CYOIO- boiling point 104 degrees 'centigrade at 0.01 millimeter; 11 1.4683.' Hydrochloride, melting point 88-90 'degrees centigrade; analysis: calculated 11.15% Cl; found 11.17% Cl.

61. 3-(1-pyrrolidyl) propyl pentylacetate a-n-butyl-a cycloboiling point 104 degrees centigrade at 0.009 millimeter; 11. 1.4688.';. Hydrochloride, melting point 98.5-102degrees centigrade; analysis: calculated 10.68% Cl; found 10.77% Cl.

62. 2-(1-pyrrolidyl) -1-methylethyl a-n-butyla-cyclopentylacetate boiling point 100 degrees centigrade at 0.01 millimeter; 71 14649. Hydrochloride, melting point 103-108. degreesv centigrade; analysis: calculated 10.68% Cl; found 10.57% Cl.

63. 2-(1-pyrrolidyl)propyl a-n-butyl-a cyclopentylacetate.

boiling point 110 degrees centigrade at 0.03 millimeter; 11 1.4700. Hydrochloride, melting point 77-81 degrees centigrade; analysis: calculated 10.68% Cl;.found 10.56% C1.

64. 2-(1-pyrrolidyl) ethyl a-n-butyl 2-cyclopentenyl) acetate a (deltaboiling point 100 degrees centigrade at 0.02 millimeter; 11, 1.4752. Citrate, meltingpoint 88-89 degrees .centigrade.

65. 3- (1-pyrrolidyl) propyl a-n-butyl-a- (delta- 2-cyclopentenyl) acetate PREPARATION 18.-5,5-DIMETHYLPYRROLIDONE-2 (HNC(CHs)2CHzCH-, CO)

A solution of 148 grams (approximately 0.845 mole) of methyl alpha-methylalpha-nitrovalerate (C2H5-CH2C(CH3) (N02) COO CH3), prepared as described in Bruson U. S. Patent 2,390,918, in approximately 500 milliliters of absolute ethanol was hydrogenated in the presence of approximately 25 grams of Raney nickelcatalyst at a temperature'of degrees centigrade and a pressure of approximately 1000 pounds per square inch gauge. The catalyst was separated by filtration, the solvent removed by distillation and the residue was heated to approximately 200 degrees centigrade and distilled at subatmospheric pressure. Its boiling point was 75 degrees centigrade at a pressure of 0.05 millimeter and it solidified in the receiver. The yield was 82.5 grams or 86.2 percent of the theoretical. A sample recrystallized from pentane had a melting point of 37-41 degrees centigrade.

Analysis-Calculated for CsHnNO: 12.38% N. Found: 11.94% N.

Another method for the preparation of 5,5- dimethylpyrrolidone-2 is described by Buckley and Elliott in J. Chem. Soc. (London) 1947, 1508.

PREPARATION 19.2,QDIMETHYLPYRBOLIDINE (HN-C CHOz-C Hr-CHz-C'Hq) A solution of 90.5 grams (approximately 0.8 mole of 5,5-dimethylpyrrolidone-2 (Preparation 18) in 200 milliliters of tetrahydrofuran was added slowly with stirring to a mixture of 38.0 grams (1 mole) of lithium aluminum hydride and 400 milliliters of tetrahydrofuran. The mixture was refluxed for 8 hours and thereafter most of the tetrahydrofuran was removed by distillation on a steam bath and was replaced by the careful addition of 300 milliliters of ether. Then 30 milliliters of water, followed by a solution of 200 milliliters of concentrated hydrochloric acid in 300 milliliters of water, was added to the mixture. The aqueous solution was extracted continuously with absolute ether for 5 hours, then made very strongly basic with sodium hydroxide and again continuously extracted with absolute ether for 12 hours. The ether extracts were dried over potassium carbonate and distilled through an efficient fractionating column to yield 62.5 grams (79 percent of the theoretical) of a colorless liquid having a boiling point of 103 degrees centigrade, 11. 1.4304 and (14. 0.82114.

Analysis-Calculated for CsHuN: 14.13% N; neutral equivalent 99.17. Found 14.12% N; neutral equivalent 99.6.

Another method for the preparation of this compound was described by Buckley and Elliott, J. Chem. Soc, 1947, 1508.

PREPARATION 20.-2- (2,2-DIMETHYL-1-1YRROLIDYL) ETHANOL Into a 500 milliliter flask, fitted with condenser, stirrer and thermometer, was placed 59.9 grams (0.6 mole) of 2,2-dimethylpyrrolidine (Preparation 19) and then 48.4 grams (0.6 mole) of ethylene chlorohydrin was added. The mixture was heated to approximately degrees centigrade to start the reaction and, after the initial reaction had subsided, it was heated to approximately to degrees centigrade for 5 minutes. The mixture was cooled and 60 milliliters of 50 percent aqueous sodium hydroxide solution was added thereto and the product was taken up in ether. The ether solution was dried over potassium carbonate and the ether was removed and the residue distilled through a short column. The yield was 62.2 grams (72.4% of the theoretical) and the product was a colorless liquid having a boiling points. of 90 degrees centigrade at a pressure of 18 millimeters, n 1.4660, 4 0.9454.

Analysis.Calculated for CsHiINOI 9.78% N; neutral equivalent 143.23. Found: 9.81% N; neutral equivalent 143.1.

PREPARATIoN 21.3,5,5-TRIMETHYLPYRROLIDONE-2 3,5,5-trimethylpyrrolidone-2 was prepared from methyl alpha,gamma-dimethyl-gamma-nitrovalerate PREPARATION 22-.2,2,4-TRIMETHYLPYRR0LIDINE EN-c oHor-cm-omoHo-om) 2,2,4-trimethylpyrrolidine was prepared from 3,5,5-trimethylpyrrolidone-2 (Preparation 21) in 85% of the theoreticalyield in a manner similar to that described for the preparation of 2,2-

dimethylpyrrolidine in Preparation 19. Its boiling point was 119 degrees centigrade at atmospheric pressure and its refractive index (11 1.4259 and its density (d4 0.8063.

Analysis-Calculated for C7H15N: 12.38% N. Found: 12.36% N.

PREPARATION 23.-2- (2,2,4-TRIMETHYI.-1-PYRR0LIDYL) ETHANOL 2-(2,2,4-trimethyl 1 pyrrolidyl) ethanol was prepared by the method described for the preparation of 2-(2,2-dimethyl-l-pyrrolidyl)ethanol in Preparation 20 from 2,2,4-trimethyl-pyrrolidine (Preparation 22) in 65.6% yield. The compound has a boiling point of 87 degrees centigrade at a pressure of 12 milliliters, n 1.4581, and d4 0.9154.

AnaZysz's.-Calculated for C9H19NO: 8.91% N. Found: 9.02% N.

PREPARATION 24.--NITRo-5-METHYLHExANoNE-2 (YCH3-'CO-1CH2-'CH2C (CH3) (N02) *CH;)

One hundred milliliters (1.28 mole) of methyl vinyl ketone was slowly added with stirring over the course of one hour to a solution of 111 milliliters (1.28 mole) of 2-nitropropane and 5 milliliters of a 40 percent aqueous solution of trimethylbenzylammonium hydroxide (Triton B) in 100 milliliters of absolute ethanol. The temperature spontaneously rose to 64 degrees. The mixture was refluxed with stirring for one hour and then diluted with ether, washed with dilute hydrochloric acid, then with dilute aqueous sodium bicarbonate solution and finally with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was removed and the product was distilled through a short column, yielding 108.9 grams (53.4 percent of the theoretical) of a light-yellow liquid having a boiling point of 119 degrees centigrade at 11 millimeters, n 1.4447 and (Z4 1.05644.

PREPARATION 25.2,2,S-TRIMETHYLPYRROLIDINE A solution of 32 grams (0.2 mole) of 5-nitro-5- methylhexanone-2 (Preparation 24) was hydrogenated in the presence of a Raney nickel catalyst at a temperature of 60 degrees centigrade and a pressure of 1000 pounds per square inch The catalyst was removed by filtration and the filtrate was distilled through a short column. The yield of 2,2,5-trimethylpyrrolidine was 11.2 grams (49.6 percent) and its boiling point was 112 degrees centigrade at atmospheric pressure, 12 1.4223, (24 0.7980.

Analysis-Calculated for C'IH15N2 12.38% N. Found: 12.38% N.

PREPARATIoN 26.-2- (2,2,5-TRIMETHYL-l-PYRRoLInYL) ETHANOL 2,2,5 trimethylpyrrolidine (Preparation 25) was reacted with ethylene chlorohydrin in the manner described for the preparation of 2-(2,2- dimethyl-l-pyrrolidyl)ethanol in Preparation 20 hereinbefore, allowing the reaction to proceed slowly and refluxing for 2 hours. The yield was 14.6 percent of the theoretical and physical constants of the product were as follows: boiling point, 86 degrees centigrade at a pressure of 11.5 millimeters; 11 1.4602; (14 0.92063.

Analysis.-Calculated for CQHIQNOI 8.91% N. Found: 8.89% N.

PREPARATION 27.2- (2,4-DIMETHYI.-3-ETHYL-1- PYRROLIDYL) ETHANOL yield was 34 percent of the theoretical,

the compound was 104-106 deat a pressure of 16 millimeters.

PREPARATION 28.2- (2-ETHYI.-1-PYRR0LIDYL) ETHANOL cm-cm-om-c cmp-N-oHr-omom 2-(2-ethyl-1-pyrrolidyl)ethanol may be made by the method described by Normant, Compt. rend. 226, 1734 (1948).

66. 2-(1-pyrrolidyl) ethyl a-phenyl-a-isobutyl acetate (CH(CH3)2CH2 'CH('CUH5) boiling point, degrees centigrade at a pressure of 0.15 millimeter; n 1.5001. Hydrochloride salt has a melting point of 995-1005 degrees centigrade.

67. 2-(1-pyrrolidyl) propyl 2-cyclopentenyl) -acetate OSH- emain) coo- JH2 oH(oH,)-NciHa) boiling point, 148 degrees centigrade at a pressure of 0.15 millimeter; 12 1.5230. The hydrochloride salt has a melting point of 123-127 degrees centigrade.

a-phenyl-adelta- 68. 2- (1-pyrrolidyl) propyl a-phenyl-a- (delta- 2-cyclohexenyl) acetate (C.H CH(CQHs)-COO-IJH 'CH (GHQ-47011218) boiling point, 147 degrees centigrade at a pressure of 0.03 millimeter; 11 1.5278. The hydrochloride has a melting point of 116-120 degrees centigrade.

69. 2 (1 pyrrolidybpropyl a-phenyl-n-cyclopentylacetate (C5H. H(C. 5)- 0 g (GHQ- mm) boiling point, 113 degrees at a pressure of 0.012 millimeter; 11 1.5157. The hydrochloride has a melting point of'105-111 degrees centigrade. 70. 2-(1-pyrrolidyl) propyl a-propyl-a-cyclopentylacetate boiling point, 90 degrees centigrade at a pressure of 0.012 millimeter; n 1.4708. Its citrate salt has a melting point of 131-132 degrees centigrade.

71. 2-(1-pyrrolidyl) -2,2-dimethylethyl a-phenyl-a.- (delta-2-cyclopentenyl) acetate s -r 6 r S)r- L Q) boiling point, 128 degrees centigrade at a pressure of 0.015 millimeter; 11 1.5220. Its citrate salt has a melting point of 103-107 degrees centigrade.

72. 2-(1-pyrrolidyl) -2,2-dimethylethyl u-phenyl-a- (delta-Z-cyclohexenyl) acetate (C H( .H6) COO-CH- (CHQF I Q) boiling point; 147 degrees centigrade at a pressure of 0.028 millimeter; 11. 1.5259. Its citrate salt has a melting point of 112-114 degrees centirade.

73. 2-(1-pyrrolidyl)'-2,Z-dimethylethyl a-(delta- 2 cyclohexenyl) a. (delta 2 cyclopentenyl) acetate (Ca -CH (CH7) -*C0 O- CH,- C (CH -NC H boiling point, 124 degrees centigrade at a pressure of 0.008 millimeter; 15 15070. The hydrochloride salt has a melting point of 117-119 degrees centigrade.

74. 2-(1-pyrrolidyl) -2,2-dimethylethyl d-"DI'O' pyl-a-cyclopentylacetate boiling point, 107 degrees centigrade at a pressure of 0.05 millimeter; 11 1.4775. Its citrate salt has a melting point of 103-1035 degrees centigrade.

75. 2-(1-pyrrolidyl) -1,2-dimethylethy1 a-phenyl-a- (delta-2-cyclopentenyl) acetate (Cs r- H(QEk)- 0 Ha)- H(CH0NCiH0 boiling point, 120 degrees centigrade ata pressure of 0.01 millimeter; 15 1.5183. The citrate salt has a melting point of 80-106 degrees centigrade.

76. 2-(1-pyrrolidyl) -1,2-dimethylethyl a.-phenyl-a- (delta -2-cyclohexenyl) acetate (C.H -CH(CHs)--C0O CH(CH;)- CH(CHs)-NC H,) boiling point, 132 degrees centigrade at a pressure of 0.012 millimeter; 11 1.5230. Its citrate salt has a melting point of 90-102 degrees centigrade.

77. 2-(1-pyrrolidyl) -1;2-diinethylethyl u- (delta- 2 cyclohexenyl) a. (delta 2 cyclopentenyl) acetate (C li -CH (CgH'I) -COOCH (CH1) CH (CH,) -NC H,) boiling point, 144 degrees centigrade at'a pressure of 0.04 millimeter; 11.5 1.5030: -=Its'- citrate salt has a melting point of 97-103 degrees centigrade.

78. 2-(1-pyrrolidyl) -1',2-dimeth'ylethyl rt-PIOIWI- a-cyclopentylacetate (CH,-CH,-CH,-CH (CBHQ) -C00- boiling point, degrees centigrade at a pressure of 0.03 millimeter; 11 14696. Its hydrochloride has a melting-point of 106.5-111 degrees centigrade.

79. 3-(1-pyrrolidyl) -2-rnethylpropyl a-phenyla- (delta-Z-cyclohexenyl) acetate (com- 0H (can-000411,- 7

ca (CH1) xii-nan.)

boiling point, 128 degrees centigrade at a'pressure of 0.01 millimeter; 11. 1.5223. Its hydrochloride has a melting point of 119-123 degrees centigrade.

80. 3-(1-pyrrolidyl) -2-methylpropyl a-PIODYI- a-cyclopentylacetate boiling point, degrees centigrade at a pressure of 0.013 millimeter; n 1.4681. Its hydrochloride has a melting point of 88-89 degrees centigrade.

81. 3-(1-pyrro1idyl) 3-methylpropyl a-phenyla- (delta-2-cyclopentenyl) acetate boiling point, 146 degrees centigrade at a pressure of 0.024 millimeter; 11, 1.5213. Its hydrochloride has a melting point of 133-136 degrees centigrade.

82. 3-(1-pyrrolidyl) -3-methylpropyl e-propyla-cyclopentenylacetate (CH,-CH H:* o)r CH: CH:CH (CH!) NCHs) boiling point, degrees centigrade at a pressure of 0.027 millimeter; n 1.4717. Its hydrochloride has a melting point of 78-80 degrees centigrade.

83. 3-(1-pyrrolidyl)-l-methylpropyl e-phenyla- (delta-Z-cyclohexenyl) acetate boiling point, 140 degrees centigrade at apressure of 0.016 millimeter; n 1.5205. Its hydrochloride has'a melting point of 153-1545 degrees centigrade.

84. 3-(1-pyrrolidyl) -1-methylpropyl a-DIOPYI- a-cyclopentylacetate (CHHH,-CH-CH(C;Ha)-COO- CH(CH;)CH,CH,NC.H.) boiling point, 135 degrees centigrade-at a pressure of 0.22 millimeter; n 1.4671. Its hydrochloride has a melting point of -127 degrees centigrade.

85. 4- (l-pyrrolidyl) butyl a-phenyl-a- (delta-2- cyclopentenyl) -acetate boiling point, 138 degrees centigrade at a pressure of 0.017 millimeter; 1L 1.5192. Its hydrochloride has a melting point of 101-103 degrees centigrade.

86. 4-(1-pyrrolidyl) butyl a-phenyl-a- (delta-2- cyclohexenyl) -acetate boiling point, 162 degrees centigrade-at apressure 29 of 0.038 millimeter; n 1.5241. Its hydrochloride has a melting point of 97-99 degrees centigrade. 87. 4 (1 pyrrolidyDbutyl a. propyl acyclopentylacetate oHs-on CH CH 'CHr-COO P CHPCHT-CHPCHZ-NQHS boiling point, 133 degrees centigrade at a pressure of 0.04 millimeter; n 1.5179. Its hydrochloride has a melting point of 116-118 degrees centigrade. 94. 2- (3,3-dimethyl-l-pyrrolidyl) ethyl a-pro- Dyl-a-cyclopentylacetate boiling point, 130 degrees centigrade at a pressure of 0.07 millimeter; n 1.4698. Its citrate has a melting point of 93.5-94.5 degrees centigrade.

88. 3- (l-pyrrolidyl) -2,2-dimethylpropyl a-DIO- pyl-a-cyclopentylacetate boiling point, 102 degrees centigrade at a pressure of 0.04 millimeter; n 1.4631. Its hydrochloride has a melting point of 107.5-108.5 degrees centigrade.

95. 2 (2,2 dimethyl 1 pyrrolidyhethyl a-PhGIlYl-adelta-2-cyclopentenyl) acetate boiling point, 131 degrees centigrade at a pressure of 0.11 millimeter; 11 1.4677. Its hydrochloride has a melting point of 134-135.5 degrees centigrade.

89. 3 (1 pyrrolidyl) 2,2 dimethylpropyl a-phenyl-a- (delta-2-cyclohexenyl) acetate boiling point, degrees centigrade at a pressure of 0.015 millimeter of mercury; n 1.5177. Its hydrochloride has a melting point of 132-142 degrees centigrade.

96. 2 (2,2 dimethyl 1 pyrrolidyl) ethyl a-phenyl-a- (delta-2-cyclohexenyl) acetate boiling point, degrees Centigrade at a pressure of 0.007 millimeter; n 1.5187.

90. 2 (3,4 dimethyl 1 pyrrolidyl) ethyl a.- n-butyl-a- (delta-2-cyclopentenyl) acetate boiling point, 134 degrees centigrade at a pressure of 0.014 millimeter; n 1.5227. Its hydrochloride has a melting point of 157-1585 degrees centigrade.

boiling point, 124 degrees centigrade at a pressure of 0.04 millimeter; n 1.4696. Its hydrochloride 97. 2 (2,2 dimethyl 1 pyrrolidyDethyl a-phenyl-a-cyclopentylacetate has a melting point of 136-1375 degrees centigrade.

91 2- (3,4-dimethyl- 1 -pyrrolidyl) ethyl pyl-a-cyclopentylacetate boiling point, degrees centigrade at a pressure of 0.065 millimeter; n 1.5109. Its hydrochloride has a melting point of 110-112 degrees centigrade.

98. 2 (2,2 dimethyl 1 pyrrolidyl) ethyl aboiling point, 95 degrees centigrade at a pressure of 0.025 millimeter; n 1.4634. Its hydrochloride (delta 2 cyclohexenyl) a (delta 2 cyclopentenyl) acetate has a melting point of 143-145 degrees centigrade.

92. 2 (2,3 dimethyl 1 pyrrohdyDethyl a-phenyl-a-'(delta-2-cyclohexenyl) acetate boiling point, 128 degrees centigrade at a pressure of 0.013 millimeter; n 1.5011. Its hydrochloride has a melting point of 130.5-132 degrees centigrade.

boiling point, 134 degrees centigrade at a pressure of 0.01 millimeter; n 1.5180. Its hydrochloride 99. 2-(2,4,4 trimethyl 1 pyrrolidyl) ethyl a.- phenyl-a (delta-Z-cyclohexenyl) acetate has a melting point of 1315-1335 degrees centigrade.

93. 2 (3,3 dimethyl 1 pyrrolidyl) ethyl aphenyl-a- (delta-2-cyclopentenyl) acetate boiling point, 136 degrees centigrade at a pressure of 0.01 millimeter; n 1.5131. Its hydrochloride has a melting point of 138-140 degrees centigrade.

31 100. 2-(2,4,4-trimetliyll-pyrrolidyllethyl a.- boiling point; 96 degrees'centigrade at expresphenyl-a-(delta-Z-cyclopentenyl) acetate sureof 0.01 millimeter; 11 1.4650.

boiling point, 130 degrees centigrade at a pres- 106. 2-'(2,2,5-trimethy1- 1 pyrrolidybethyl asure of 0.02 millimeter; 11. 1.5079. Its hydrophenyl-a-(delta-2-cycl0pentenyl) acetate chloride'has a melting point of 140-141 degrees boiling point, 136 degrees centigrade at a, prescentigrade. sure of- 0.04 millimeter;- n 1.5138. Its'hydro- 101. 2-(2,4,4-trimethyl 1 pyrrolidyl) ethyl achloride has a melting point of 108-112 degrees propyl-a-eyclopentylacetate centigrade. (C1H-;CH(C5HQ)COO-CBz-CHzN-OH(CH3)-CH1O(CHM-CH1) boiling point, 99 degrees centigrade at a pressure 107. 2-(2,2,5-trimethyl 1 pyrrolidyl) ethyl noi '0.015 millimeter; 11 1.4610. Its hydrochlopropyl-a-cyclopentylacetate ride has a melting point of 1455-1465 degrees boiling point, 107 degrees centigrade at a prescentigrade. sure of 0:028 millimeter; 15 1.4660. I Its'hydro- 102. 2-(2,4,4-trimethyl 1 pyrrolidyl) ethyl achloride has a melting point of -975 degrees (delta-Z-cyclopentenyl) a. -(delta-2-cyc1ohexencentigrade.

yDacetate boiling point, 128 degrees centigrade at a pres- 108. 2-(2-ethyl-1-pyrrolidyl)ethyl a-phBIlYl-asure of 0.015 millimeter, 11 1.4932. Its hydro- (delta-Z-cyclopentenyl)acetate chloride has a. melting point of 137-138 degrees boiling point, 132 degrees centigrade at a. prescentigrade. sure of 0.03 millimeter; 11 1.5179. Its hydro- 103. 2-(2,2,4-trimethy1- 1 pyrrolidyDethyl achloride has a melting point of -125 degrees phenyl-a- (delta-Z-cyclohexenyl) acetate centigrade.

boiling point, degrees centigrade at a pres- "109. 2-(2-ethyl-1-pyrrolidyl) ethyl a-pheny1asure of 0.045 millimeter; 11. 1.5170. Its hydro- (delta-2-cyclohexenyl)acetate chloride-has a melting point of 148.5-150 degrees boiling point, 147 degrees centigrade at a prescentigrade. sure of 0.02 millimeter; n 1.5227. Its hydro- .104. 2-(2,2,4-trimethyl 1 pyrrolidyhethyl achloride has a melting point of 146.5-149 degrees phenyl-a- (delta-2-cyclopentenyl) acetate centigrade.

boiling point, 132 degrees Centigrade at a pres- 110.-2-(2-ethyl-1-pyrrolidyl) ethyl a-plopyl-asure of 0.02 millimeter; n 1.5117. Its hydrocyclopentylacetate chloride-has a melting point of 153-1565 degrees boiling point, 104 degrees Centigrade at a prescentigraxie. sure of 0.02 millimeter; n 1,4635 t hydro- 105. 2-(2,2,4-trimethyl 1 pyrrolidyl) ethyl achloride has .a. melting point of 96.5-98.5 degrees propyl-a-cyclopentylacetate centigrade.

& 111. 2-(2-ethyl-1-pyrrolidyl) ethyl a-phenyl-acyclopentylacetate radical containing a om five to six carbon monocyclic hydrocarbon carbocyclic ring having fr boiling point, 126 degrees centigrade at a pressure of 0.015 millimeter; n 1.5110. Its hydrochloride has a melting point of 138-144 degrees centigrade.

112. 2-(2,4-dimethyl-3-ethyl-1 yl a-propyl-a-cyclopentylacetate -pyrrolidyl) ethboiling point, 129 degrees centigrade at a pressure of 0.01 millimeter; n 1.4608. Its hydrochloride has a melting point of 109-112 degrees centigrade.

Various modifications may be made in the compounds of the present invention without departing from the spirit or scope thereof, and it is to be understood that I limit myself only as defined in the appended claims.

I claim:

1. A compound sel ected from the group con- 15 (b) acid addition and (o) quaternary ammonium salts thereof.

2. 2-(2-methyl-1-pyrrolidyl) ethyl alpha-phenyl-alpha- (delta-2-cyclohexenyl) acetate.

3. 2-(2,2-dimethyl-l-pyrrolidyl) ethyl alpha-n- 0 propyl alpha-cyclopentylacetate hydrochloride.

4. 2-(2,2-dimethyl-l-pyrrolidyl) ethyl alpha-npropyl-alpha-cyclopentylacetate methobromide. 5. 2-(Z-methyl-l-pyrrolidyl) ethyl alpha-phenyl-alpha-cyclopenty1acetate hydrochloride.

6. 2- l-pyrrclidyl) ethyl alpha-phenyl-alpha- 25 sis in of (a) (l-pyrrolidybalkyl e t r p (delta-Z-cyclopentenyl)acetate ethobromide. sented by the following formula:

(lower-alkyl). EUGENE H. WOODRUFF. g l O 30 References Cited in the file of this patent i' UNITED STATES PATENTS Z C Number Name Date w n X is elected from the group consisting 2 541 34 Blicke 13, 9

of hydrogen and lower-alkyl radicals, Y is a 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF (A) (1-PYRROLIDYL) ALKYL ESTERS REPRESENTED BY THE FOLLOWING FORMULA: 